We propose to investigate the role of pp60c-src, the cellular homolog of pp60v-src the transforming protein of Rous sarcoma virus, in cellular growth control. We will focus on determining whether pp60v-src induced neoplastic transformation represents the effect of overexpression of an essentially normal cellular protein or if it represents the effect of functional differences between the viral and cellular proteins. We will complete our current program which is designed to generate pp60c-src overexpressing cells in the absence of selection for neoplastic transformation by the use of the cloned cellular src gene, viral transcriptional promoters and dominant biologically coselectable markers. These cells will be used to determine if overexpression of authentic pp60c-src induces neoplastic transformation. If overexpression of pp60c-src does induce transformation, we will investigate the dose-response effect of pp60c-src and look for differences and correlations between the biochemical and biological activities of overexpressed pp60c-src and pp60v-src in a range of genetically transformed cell species and types to determine which activities are required for transformation. If overexpression of pp60c-src does not induce transformation, we will determine which structural and functional alterations in pp60v-src are responsible for transformation by creating c-src - v-src recombinant transformation genes and assaying their biological and biochemical activities and by sequencing the cellular src coding sequence. If pp60c-src overexpressing cells cannot be generated, we will generate recombinant pp60r-src proteins by genetic manipulations and use them to explore the effects of the structural differences between the cellular and viral proteins. These studies in the molecular and cell biology of cellular transformation and growth control should, in the long term, contribute to elucidating the molecular basis of neoplastic disease.